USC Alzheimer Disease Research Center Epidemiologic studies have long observed associations between highly prevalent and treatable vascular risk factors and an increased incidence of AD, yet the causative mechanisms are unclear. During the past 4 years, USC has made incremental strides in developing neuroselective steroids for the prevention and treatment of AD. A major Provost hiring initiative in neuroscience has brought together a critical mass of scientific talent in Alzheimer disease, especially knowledgeable about the cerebral vasculature, neuroimaging, and Phase I/ II clinical trials. The USC ADRC is an integral part of the national Alzheimer Disease Center (ADC) network, working closely with the National Alzheimer Coordinating Center (NACC), Alzheimer Cooperative Studies (ADCS), the Alzheimer Disease Genetics Consortium (ADGC), and Alzheimer Disease Neuroimaging Initiative (ADNI). Accordingly, the USC ADRC has three unique overarching goals: 1) elucidate vascular contributions to Alzheimer's disease (AD); 2) catalyze local research in AD at USC (especially Phase I/Phase II clinical trials); and 3) contribute expertise in vascular disease and imaging to national collaborative initiatives. The Administrative Core (Chui & Zlokovic) is responsible for the overall scientific direction of the center and the coordination of 5 service Cores, 2 research projects, and 2-3 pilot projects per year. The Clinical core (Schneider), assisted by the Outreach core (Williams), will constitute and follow a new vascular cohort (n-180) to support Projects 1 and 2, and will refer well-characterized participants to clinical trials, the brain donation (autopsy) program, and other research projects. The Imaging core (Law, Toga, Thompson) offers innovations in imaging the integrity of the blood brain barrier (DCE-MRI), white matter fiber tracts (DTI-MRI), and functional connectivity (fMRI). The Neuropathology core (Miller), which characterizes and shares brain tissues and biospecimens, will provide a comprehensive panel of CSF biomarkers. Project 1 ( Zlokovic) and Project 2 (Braskie) share a complementary focus on the role of Neurovascular and Metabolic Factors on AD pathogenesis, thereby giving scientific cohesiveness to the Center as a whole. The Data core (Toga) will make available on line and without embargo, the imaging, biomarker, and clinical-pathological data from ADRC participants. Thus, the USC ADRC is prepared to serve as the nexus for translational research at USC and to bring unique resources to the national ADC research enterprise.